Toll-like Receptor as a Molecular Link between Metabolic Syndrome and Inflammation: A Review

Author(s): Sok Kuan Wong , Kok-Yong Chin , Soelaiman Ima-Nirwana* .

Journal Name: Current Drug Targets

Volume 20 , Issue 12 , 2019

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Metabolic Syndrome (MetS) involves a cluster of five conditions, i.e. obesity, hyperglycaemia, hypertension, hypertriglyceridemia and low High-Density Lipoprotein (HDL) cholesterol. All components of MetS share an underlying chronic inflammatory aetiology, manifested by increased levels of pro-inflammatory cytokines. The pathogenic role of inflammation in the development of MetS suggested that toll-like receptor (TLR) activation may trigger MetS. This review summarises the supporting evidence on the interactions between MetS and TLR activation, bridged by the elevation of TLR ligands during MetS. The regulatory circuits mediated by TLR activation, which modulates signal propagation, leading to the state of chronic inflammation, are also discussed. Taken together, TLR activation could be the molecular basis in the development of MetS-induced inflammation.

Keywords: Cytokine, free fatty acids, heat shock protein, interleukin, interferon, tumour necrosis factor.

[1]
Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120(16): 1640-5.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.192644] [PMID: 19805654]
[2]
Ramli AS, Daher AM, Nor-Ashikin MN, et al. JIS definition identified more Malaysian adults with metabolic syndrome compared to the NCEP-ATP III and IDF criteria. BioMed Res Int 2013; 2013760963
[http://dx.doi.org/10.1155/2013/760963] [PMID: 24175300]
[3]
Srikanthan K, Feyh A, Visweshwar H, Shapiro JI, Sodhi K. Systematic review of metabolic syndrome biomarkers: A panel for early detection, management, and risk stratification in the west virginian population. Int J Med Sci 2016; 13(1): 25-38.
[http://dx.doi.org/10.7150/ijms.13800] [PMID: 26816492]
[4]
Gao W, Xiong Y, Li Q, Yang H. Inhibition of toll-like receptor signaling as a promising therapy for inflammatory diseases: A journey from molecular to nano therapeutics. Front Physiol 2017; 8: 508.
[http://dx.doi.org/10.3389/fphys.2017.00508] [PMID: 28769820]
[5]
Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol 2014; 5: 461.
[http://dx.doi.org/10.3389/fimmu.2014.00461] [PMID: 25309543]
[6]
Li J, Lee DS, Madrenas J. Evolving bacterial envelopes and plasticity of TLR2-dependent responses: Basic research and translational opportunities. Front Immunol 2013; 4: 347.
[http://dx.doi.org/10.3389/fimmu.2013.00347] [PMID: 24191155]
[7]
Jialal I, Huet BA, Kaur H, Chien A, Devaraj S. Increased toll-like receptor activity in patients with metabolic syndrome. Diabetes Care 2012; 35(4): 900-4.
[http://dx.doi.org/10.2337/dc11-2375] [PMID: 22357188]
[8]
Devaraj S, Dasu MR, Park SH, Jialal I. Increased levels of ligands of Toll-like receptors 2 and 4 in type 1 diabetes. Diabetologia 2009; 52(8): 1665-8.
[http://dx.doi.org/10.1007/s00125-009-1394-8] [PMID: 19455302]
[9]
Creely SJ, McTernan PG, Kusminski CM, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab 2007; 292(3): E740-7.
[http://dx.doi.org/10.1152/ajpendo.00302.2006] [PMID: 17090751]
[10]
Dasu MR, Devaraj S, Park S, Jialal I. Increased toll-like receptor (TLR) activation and TLR ligands in recently diagnosed type 2 diabetic subjects. Diabetes Care 2010; 33(4): 861-8.
[http://dx.doi.org/10.2337/dc09-1799] [PMID: 20067962]
[11]
Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007; 56(7): 1761-72.
[http://dx.doi.org/10.2337/db06-1491] [PMID: 17456850]
[12]
Zhou X, Han D, Xu R, et al. A model of metabolic syndrome and related diseases with intestinal endotoxemia in rats fed a high fat and high sucrose diet. PLoS One 2014; 9(12)e115148
[http://dx.doi.org/10.1371/journal.pone.0115148] [PMID: 25502558]
[13]
Suzuki T, Hara H. Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats. Nutr Metab (Lond) 2010; 7: 19.
[http://dx.doi.org/10.1186/1743-7075-7-19] [PMID: 20222989]
[14]
Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 2007; 104(3): 979-84.
[http://dx.doi.org/10.1073/pnas.0605374104] [PMID: 17210919]
[15]
Kaliannan K, Hamarneh SR, Economopoulos KP, et al. Intestinal alkaline phosphatase prevents metabolic syndrome in mice. Proc Natl Acad Sci USA 2013; 110(17): 7003-8.
[http://dx.doi.org/10.1073/pnas.1220180110] [PMID: 23569246]
[16]
Jialal I, Rajamani U, Adams-Huet B, Kaur H. Circulating pathogen-associated molecular pattern - binding proteins and High Mobility Group Box protein 1 in nascent metabolic syndrome: implications for cellular Toll-like receptor activity. Atherosclerosis 2014; 236(1): 182-7.
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.06.022] [PMID: 25063948]
[17]
Reyna SM, Ghosh S, Tantiwong P, et al. Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. Diabetes 2008; 57(10): 2595-602.
[http://dx.doi.org/10.2337/db08-0038] [PMID: 18633101]
[18]
Devaraj S, Dasu MR, Rockwood J, Winter W, Griffen SC, Jialal I. Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: further evidence of a proinflammatory state. J Clin Endocrinol Metab 2008; 93(2): 578-83.
[http://dx.doi.org/10.1210/jc.2007-2185] [PMID: 18029454]
[19]
Devaraj S, Jialal I, Yun JM, Bremer A. Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications. Metabolism 2011; 60(2): 256-9.
[http://dx.doi.org/10.1016/j.metabol.2010.01.005] [PMID: 20153491]
[20]
Cha JJ, Hyun YY, Lee MH, et al. Renal protective effects of toll-like receptor 4 signaling blockade in type 2 diabetic mice. Endocrinology 2013; 154(6): 2144-55.
[http://dx.doi.org/10.1210/en.2012-2080] [PMID: 23568555]
[21]
Wang C, Ha X, Li W, et al. Correlation of TLR4 and KLF7 in Inflammation Induced by Obesity. Inflammation 2017; 40(1): 42-51.
[http://dx.doi.org/10.1007/s10753-016-0450-z] [PMID: 27714571]
[22]
Kim SJ, Choi Y, Choi YH, Park T. Obesity activates toll-like receptor-mediated proinflammatory signaling cascades in the adipose tissue of mice. J Nutr Biochem 2012; 23(2): 113-22.
[http://dx.doi.org/10.1016/j.jnutbio.2010.10.012] [PMID: 21414767]
[23]
Himes RW, Smith CW. Tlr2 is critical for diet-induced metabolic syndrome in a murine model. FASEB J 2010; 24(3): 731-9.
[http://dx.doi.org/10.1096/fj.09-141929] [PMID: 19841034]
[24]
Izumi T. Adipose cell and lipid turnovers in obesity and insulin resistance. Diabetol Int 2012; 3(4): 184-6.
[http://dx.doi.org/10.1007/s13340-012-0092-9]
[25]
Zwolak A, Słabczyńska O, Semeniuk J, Daniluk J, Szuster-Ciesielska A. Metformin Changes the Relationship between Blood Monocyte Toll-Like Receptor 4 Levels and Nonalcoholic Fatty Liver Disease-Ex Vivo Studies. PLoS One 2016; 11(3)e0150233
[http://dx.doi.org/10.1371/journal.pone.0150233] [PMID: 26930651]
[26]
Liao YR, Li ZJ, Zeng P, Lan YQ. TLR7 deficiency contributes to attenuated diabetic retinopathy via inhibition of inflammatory response. Biochem Biophys Res Commun 2017; 493(2): 1136-42.
[http://dx.doi.org/10.1016/j.bbrc.2017.08.085] [PMID: 28843858]
[27]
Singh VP, Bali A, Singh N, Jaggi AS. Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol 2014; 18(1): 1-14.
[http://dx.doi.org/10.4196/kjpp.2014.18.1.1] [PMID: 24634591]
[28]
Wang Y, Zhong J, Zhang X, et al. The Role of HMGB1 in the Pathogenesis of Type 2 Diabetes. J Diabetes Res 2016; •••20162543268
[http://dx.doi.org/10.1155/2016/2543268] [PMID: 28101517]
[29]
Szasz T, Wenceslau CF, Burgess B, Nunes KP, Webb RC. Toll-Like Receptor 4 Activation Contributes to Diabetic Bladder Dysfunction in a Murine Model of Type 1 Diabetes. Diabetes 2016; 65(12): 3754-64.
[http://dx.doi.org/10.2337/db16-0480] [PMID: 27650857]
[30]
Dange RB, Agarwal D, Teruyama R, Francis J. Toll-like receptor 4 inhibition within the paraventricular nucleus attenuates blood pressure and inflammatory response in a genetic model of hypertension. J Neuroinflammation 2015; 12: 31.
[http://dx.doi.org/10.1186/s12974-015-0242-7] [PMID: 25879545]
[31]
Zhang J, Zhang L, Zhang S, et al. HMGB1, an innate alarmin, plays a critical role in chronic inflammation of adipose tissue in obesity. Mol Cell Endocrinol 2017; 454: 103-11.
[http://dx.doi.org/10.1016/j.mce.2017.06.012] [PMID: 28619625]
[32]
Sevin M, Girodon F, Garrido C, de Thonel A. HSP90 and HSP70: Implication in Inflammation Processes and Therapeutic Approaches for Myeloproliferative Neoplasms. Mediators Inflamm 2015.2015970242
[http://dx.doi.org/10.1155/2015/970242] [PMID: 26549943]
[33]
Noble EG, Shen GX. Impact of exercise and metabolic disorders on heat shock proteins and vascular inflammation. Autoimmune Dis 2012.2012836519
[http://dx.doi.org/10.1155/2012/836519] [PMID: 23304460]
[34]
Zhao R, Shen GX. Involvement of heat shock factor-1 in glycated LDL-induced upregulation of plasminogen activator inhibitor-1 in vascular endothelial cells. Diabetes 2007; 56(5): 1436-44.
[http://dx.doi.org/10.2337/db06-1199] [PMID: 17259369]
[35]
Fakhari A, Berkland C. Applications and emerging trends of hyaluronic acid in tissue engineering, as a dermal filler and in osteoarthritis treatment. Acta Biomater 2013; 9(7): 7081-92.
[http://dx.doi.org/10.1016/j.actbio.2013.03.005] [PMID: 23507088]
[36]
Kang L, Lantier L, Kennedy A, et al. Hyaluronan accumulates with high-fat feeding and contributes to insulin resistance. Diabetes 2013; 62(6): 1888-96.
[http://dx.doi.org/10.2337/db12-1502] [PMID: 23349492]
[37]
Drexler SK, Foxwell BM. The role of toll-like receptors in chronic inflammation. Int J Biochem Cell Biol 2010; 42(4): 506-18.
[http://dx.doi.org/10.1016/j.biocel.2009.10.009] [PMID: 19837184]
[38]
Devaraj S, Adams-Huet B, Jialal I. Endosomal Toll-Like Receptor Status in Patients with Metabolic Syndrome. Metab Syndr Relat Disord 2015; 13(10): 477-80.
[http://dx.doi.org/10.1089/met.2015.0116] [PMID: 26505293]
[39]
Hardy OT, Kim A, Ciccarelli C, Hayman LL, Wiecha J. Increased Toll-like receptor (TLR) mRNA expression in monocytes is a feature of metabolic syndrome in adolescents. Pediatr Obes 2013; 8(1): e19-23.
[http://dx.doi.org/10.1111/j.2047-6310.2012.00098.x] [PMID: 22991262]
[40]
Ahmad R, Al-Mass A, Atizado V, et al. Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation. J Inflamm (Lond) 2012; 9(1): 48.
[http://dx.doi.org/10.1186/1476-9255-9-48] [PMID: 23191980]
[41]
Ahmad R, Kochumon S, Thomas R, Atizado V, Sindhu S. Increased adipose tissue expression of TLR8 in obese individuals with or without type-2 diabetes: significance in metabolic inflammation. J Inflamm (Lond) 2016; 13: 38.
[http://dx.doi.org/10.1186/s12950-016-0147-y] [PMID: 27980459]
[42]
Marketou ME, Kontaraki JE, Zacharis EA, et al. TLR2 and TLR4 gene expression in peripheral monocytes in nondiabetic hypertensive patients: the effect of intensive blood pressure-lowering. J Clin Hypertens (Greenwich) 2012; 14(5): 330-5.
[http://dx.doi.org/10.1111/j.1751-7176.2012.00620.x] [PMID: 22533660]
[43]
Yki-Järvinen H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol 2014; 2(11): 901-10.
[http://dx.doi.org/10.1016/S2213-8587(14)70032-4] [PMID: 24731669]
[44]
Kanuri G, Ladurner R, Skibovskaya J, et al. Expression of toll-like receptors 1-5 but not TLR 6-10 is elevated in livers of patients with non-alcoholic fatty liver disease. Liver international : official journal of the International Association for the Study of the Liver 2015; 35(2): 562-8.
[45]
Davis JE, Braucher DR, Walker-Daniels J, Spurlock ME. Absence of Tlr2 protects against high-fat diet-induced inflammation and results in greater insulin-stimulated glucose transport in cultured adipocytes. J Nutr Biochem 2011; 22(2): 136-41.
[http://dx.doi.org/10.1016/j.jnutbio.2009.12.008] [PMID: 20434320]
[46]
He W, Yuan T, Choezom D, et al. Ageing potentiates diet-induced glucose intolerance, β-cell failure and tissue inflammation through TLR4. Sci Rep 2018; 8(1): 2767.
[http://dx.doi.org/10.1038/s41598-018-20909-w] [PMID: 29426925]
[47]
Devaraj S, Tobias P, Kasinath BS, Ramsamooj R, Afify A, Jialal I. Knockout of toll-like receptor-2 attenuates both the proinflammatory state of diabetes and incipient diabetic nephropathy. Arterioscler Thromb Vasc Biol 2011; 31(8): 1796-804.
[http://dx.doi.org/10.1161/ATVBAHA.111.228924] [PMID: 21617141]
[48]
Ma J, Wu H, Zhao CY, Panchapakesan U, Pollock C, Chadban SJ. Requirement for TLR2 in the development of albuminuria, inflammation and fibrosis in experimental diabetic nephropathy. Int J Clin Exp Pathol 2014; 7(2): 481-95.
[PMID: 24551269]
[49]
Shao YX, Xu XX, Wang K, Qi XM, Wu YG. Paeoniflorin attenuates incipient diabetic nephropathy in streptozotocin-induced mice by the suppression of the Toll-like receptor-2 signaling pathway. Drug Des Devel Ther 2017; 11: 3221-33.
[http://dx.doi.org/10.2147/DDDT.S149504] [PMID: 29184392]
[50]
Ma J, Chadban SJ, Zhao CY, et al. TLR4 activation promotes podocyte injury and interstitial fibrosis in diabetic nephropathy. PLoS One 2014; 9(5)e97985
[http://dx.doi.org/10.1371/journal.pone.0097985] [PMID: 24842252]
[51]
Ghosh AK, O’Brien M, Mau T, Yung R. Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging. Aging (Albany NY) 2017; 9(9): 1971-82.
[http://dx.doi.org/10.18632/aging.101288] [PMID: 28898202]
[52]
Li D, Wang X, Lan X, et al. Down-regulation of miR-144 elicits proinflammatory cytokine production by targeting toll-like receptor 2 in nonalcoholic steatohepatitis of high-fat-diet-induced metabolic syndrome E3 rats. Mol Cell Endocrinol 2015; 402: 1-12.
[http://dx.doi.org/10.1016/j.mce.2014.12.007] [PMID: 25534427]
[53]
Ballak DB, van Asseldonk EJ, van Diepen JA, et al. TLR-3 is present in human adipocytes, but its signalling is not required for obesity-induced inflammation in adipose tissue in vivo. PLoS One 2015; 10(4)e0123152
[http://dx.doi.org/10.1371/journal.pone.0123152] [PMID: 25867514]
[54]
Vijay-Kumar M, Aitken JD, Carvalho FA, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 2010; 328(5975): 228-31.
[http://dx.doi.org/10.1126/science.1179721] [PMID: 20203013]
[55]
Hong CP, Yun CH, Lee GW, Park A, Kim YM, Jang MH. TLR9 regulates adipose tissue inflammation and obesity-related metabolic disorders. Obesity (Silver Spring) 2015; 23(11): 2199-206.
[http://dx.doi.org/10.1002/oby.21215] [PMID: 26260403]
[56]
Durrer C, Francois M, Neudorf H, Little JP. Acute high-intensity interval exercise reduces human monocyte Toll-like receptor 2 expression in type 2 diabetes. Am J Physiol Regul Integr Comp Physiol 2017; 312(4): R529-38.
[http://dx.doi.org/10.1152/ajpregu.00348.2016] [PMID: 28122717]
[57]
Han LP, Li CJ, Sun B, et al. Protective Effects of Celastrol on Diabetic Liver Injury via TLR4/MyD88/NF-κB Signaling Pathway in Type 2 Diabetic Rats. J Diabetes Res 2016; •••20162641248
[http://dx.doi.org/10.1155/2016/2641248] [PMID: 27057550]
[58]
Eraky SM, Abdel-Rahman N, Eissa LA. Modulating effects of omega-3 fatty acids and pioglitazone combination on insulin resistance through toll-like receptor 4 in type 2 diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids 2017.
[PMID: 28716464]
[59]
Bhaskar S, Helen A. Quercetin modulates toll-like receptor-mediated protein kinase signaling pathways in oxLDL-challenged human PBMCs and regulates TLR-activated atherosclerotic inflammation in hypercholesterolemic rats. Mol Cell Biochem 2016; 423(1-2): 53-65.
[http://dx.doi.org/10.1007/s11010-016-2824-9] [PMID: 27665434]
[60]
Francisqueti FV, Nascimento AF, Minatel IO, et al. Metabolic syndrome and inflammation in adipose tissue occur at different times in animals submitted to a high-sugar/fat diet. J Nutr Sci 2017; 6e41
[http://dx.doi.org/10.1017/jns.2017.42] [PMID: 29152245]
[61]
Suganami T, Mieda T, Itoh M, Shimoda Y, Kamei Y, Ogawa Y. Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation. Biochem Biophys Res Commun 2007; 354(1): 45-9.
[http://dx.doi.org/10.1016/j.bbrc.2006.12.190] [PMID: 17210129]
[62]
Ding Y, Subramanian S, Montes VN, et al. Toll-like receptor 4 deficiency decreases atherosclerosis but does not protect against inflammation in obese low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol 2012; 32(7): 1596-604.
[http://dx.doi.org/10.1161/ATVBAHA.112.249847] [PMID: 22580897]
[63]
Feng Y, Yang S, Ma Y, Bai XY, Chen X. Role of Toll-like receptors in diabetic renal lesions in a miniature pig model. Sci Adv 2015; 1(5)e1400183
[http://dx.doi.org/10.1126/sciadv.1400183] [PMID: 26601192]
[64]
Zou ZY, Hu YR, Ma H, et al. Coptisine attenuates obesity-related inflammation through LPS/TLR-4-mediated signaling pathway in Syrian golden hamsters. Fitoterapia 2015; 105: 139-46.
[http://dx.doi.org/10.1016/j.fitote.2015.06.005] [PMID: 26073947]
[65]
Chen S, Lin G, Lei L, et al. Hyperlipidemia modifies innate immune responses to lipopolysaccharide via the TLR-NF-κB signaling pathway. Inflammation 2013; 36(4): 968-76.
[http://dx.doi.org/10.1007/s10753-013-9628-9] [PMID: 23504260]
[66]
Wang H, Zhang Q, Chai Y, et al. 1,25(OH)2D3 downregulates the Toll-like receptor 4-mediated inflammatory pathway and ameliorates liver injury in diabetic rats. J Endocrinol Invest 2015; 38(10): 1083-91.
[http://dx.doi.org/10.1007/s40618-015-0287-6] [PMID: 25906757]
[67]
Xu XX, Qi XM, Zhang W, et al. Effects of total glucosides of paeony on immune regulatory toll-like receptors TLR2 and 4 in the kidney from diabetic rats. Phytomedicine : international journal of phytotherapy and phytopharmacology 2014; 21(6): 815-23.
[http://dx.doi.org/10.1016/j.phymed.2013.12.003]
[68]
Li F, Zhang N, Li Z, Deng L, Zhang J, Zhou Y. Toll-like receptor 2 agonist exacerbates renal injury in diabetic mice. Exp Ther Med 2017; 13(2): 495-502.
[http://dx.doi.org/10.3892/etm.2017.4031] [PMID: 28352321]
[69]
Ji YY, Liu JT, Liu N, Wang ZD, Liu CH. PPARalpha activator fenofibrate modulates angiotensin II-induced inflammatory responses in vascular smooth muscle cells via the TLR4-dependent signaling pathway. Biochem Pharmacol 2009; 78(9): 1186-97.
[http://dx.doi.org/10.1016/j.bcp.2009.06.095] [PMID: 19576184]
[70]
Hernanz R, Martínez-Revelles S, Palacios R, et al. Toll-like receptor 4 contributes to vascular remodelling and endothelial dysfunction in angiotensin II-induced hypertension. Br J Pharmacol 2015; 172(12): 3159-76.
[http://dx.doi.org/10.1111/bph.13117] [PMID: 25712370]
[71]
Dange RB, Agarwal D, Masson GS, et al. Central blockade of TLR4 improves cardiac function and attenuates myocardial inflammation in angiotensin II-induced hypertension. Cardiovasc Res 2014; 103(1): 17-27.
[http://dx.doi.org/10.1093/cvr/cvu067] [PMID: 24667851]
[72]
Young KC, Hussein SM, Dadiz R, et al. Toll-like receptor 4-deficient mice are resistant to chronic hypoxia-induced pulmonary hypertension. Exp Lung Res 2010; 36(2): 111-9.
[http://dx.doi.org/10.3109/01902140903171610] [PMID: 20205596]
[73]
Nair AR, Elks CM, Vila J, Del Piero F, Paulsen DB, Francis J. A blueberry-enriched diet improves renal function and reduces oxidative stress in metabolic syndrome animals: potential mechanism of TLR4-MAPK signaling pathway. PLoS One 2014; 9(11)e111976
[http://dx.doi.org/10.1371/journal.pone.0111976] [PMID: 25372283]
[74]
Zhang T, Zhu Q, Shao Y, Wang K, Wu Y. Paeoniflorin prevents TLR2/4-mediated inflammation in type 2 diabetic nephropathy. Biosci Trends 2017; 11(3): 308-18.
[http://dx.doi.org/10.5582/bst.2017.01104] [PMID: 28626209]
[75]
Bomfim GF, Dos Santos RA, Oliveira MA, et al. Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats Clinical science (London, England : 1979) 2012; 122(11): 535-43.
[http://dx.doi.org/]
[76]
Bomfim GF, Echem C, Martins CB, et al. Toll-like receptor 4 inhibition reduces vascular inflammation in spontaneously hypertensive rats. Life Sci 2015; 122: 1-7.
[http://dx.doi.org/10.1016/j.lfs.2014.12.001] [PMID: 25498891]
[77]
Echem C, Bomfim GF, Ceravolo GS, et al. Anti-toll like receptor 4 (TLR4) therapy diminishes cardiac remodeling regardless of changes in blood pressure in spontaneously hypertensive rats (SHR). Int J Cardiol 2015; 187: 243-5.
[http://dx.doi.org/10.1016/j.ijcard.2015.03.190] [PMID: 25838224]
[78]
Eißler R, Schmaderer C, Rusai K, et al. Hypertension augments cardiac Toll-like receptor 4 expression and activity Hypertension research : official journal of the Japanese Society of Hypertension 2011; 34(5): 551-8.
[79]
Li HB, Li X, Huo CJ, et al. TLR4/MyD88/NF-κB signaling and PPAR-γ within the paraventricular nucleus are involved in the effects of telmisartan in hypertension. Toxicol Appl Pharmacol 2016; 305: 93-102.
[http://dx.doi.org/10.1016/j.taap.2016.06.014] [PMID: 27292124]
[80]
Lavanya V, Mohamed Adil AA, Ahmed N, Rishi AK, Jamal S. Small molecule inhibitors as emerging cancer therapeutics. Integr Cancer Sci Ther 2014; 1(3): 39-46.
[81]
Cui G, Ye X, Zuo T, et al. Chloroquine pretreatment inhibits toll-like receptor 3 signaling after stroke. Neurosci Lett 2013; 548: 101-4.
[http://dx.doi.org/10.1016/j.neulet.2013.02.072] [PMID: 23558035]
[82]
Gomez-Guzman M, Jimenez R, Romero M, et al. Chronic hydroxychloroquine improves endothelial dysfunction and protects kidney in a mouse model of systemic lupus erythematosus. Hypertension(Dallas, Tex : 1979) 2014; 64(2): 330-7.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03587]
[83]
Fang D, Yang S, Quan W, Jia H, Quan Z, Qu Z. Atorvastatin suppresses Toll-like receptor 4 expression and NF-κB activation in rabbit atherosclerotic plaques. Eur Rev Med Pharmacol Sci 2014; 18(2): 242-6.
[PMID: 24488914]
[84]
Moutzouri E, Tellis CC, Rousouli K, et al. Effect of simvastatin or its combination with ezetimibe on Toll-like receptor expression and lipopolysaccharide-induced cytokine production in monocytes of hypercholesterolemic patients. Atherosclerosis 2012; 225(2): 381-7.
[http://dx.doi.org/10.1016/j.atherosclerosis.2012.08.037] [PMID: 23062767]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 12
Year: 2019
Page: [1264 - 1280]
Pages: 17
DOI: 10.2174/1389450120666190405172524
Price: $58

Article Metrics

PDF: 19
HTML: 2
EPUB: 1
PRC: 1